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The role of mitochondrial dynamics in cell death
Novotná, Eliška ; Rohlena, Jakub (advisor) ; Alán, Lukáš (referee)
Mitochondria form a dynamic reticulum, which fragments in apoptosis. It is assumed that proteins of mitochondrial dynamics participate in the intrinsic pathway of apoptosis and remodel mitochondrial membranes to release cytochrome c to the cytosol. The most important role in this process is played by Opa1, a protein involved in mitochondrial fusion, and by Drp1, which induces mitochondrial fission. During apoptosis, Opa1 remodels cristae in the inner mitochondrial membrane, which is crucial for effective release of cytochrome c to the cytosol. The role of Drp1 is less clear and is a subject of intense debate. Upon initiation of apoptosis Drp1 is recruited to mitochondria where it facilitates apoptotic pore formation and triggers fission. However, it appears that recruitment of Drp1 is not absolutely required for successful execution of apoptosis. In addition, mitochondrial dynamics is influenced by Bcl-2 family proteins. Recruitment of proapoptotic Bcl-2 proteins to mitochondrial outer membrane leads to inhibition of mitochondrial fusion, which enhances fragmented morphology of mitochondria. Although mitochondrial fragmentation in apoptosis is known for decades, its precise purpose remains to be elucidated.
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